MassIVEapplication/xmlftp://massive.ucsd.edu/v05/MSV000090744/primaryOK200Diana Hargreaveshttps://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=63becd806f68431c90cb6455e5e7ec12dhargreaves@salk.eduMassIVE30MS:1002864 - No post-translational-modifications are included in the identified peptides of this datasetProteomicsOrbitrap Fusion LumosMus Musculus (ncbitaxon:10090)Salk Institutepancreatic adenocarcinoma, Epigenetic, Dmikkgamma, IKK-gamma, pancreas adenocarcinoma, CG16910, dIKK-gamma, Epigenomic, adenocarcinoma of pancreas, IKKgamma, adenocarcinoma - pancreas., DmIKKgamma, DmelCG16910, adenocarcinoma of the pancreas, IKK, dIKK, DmIKK-gamma, Kenny, PAAD, dmIKKgamma, IKK[[gamma]], Epigenetics, IKKg, KEY, Keybiochemical pathways, malignant Growth, HNF3-alpha, SNF2LT, type 2, Metabolic Process, baf, Materials, insensitive, DmelCG4528, exocrine cancer, determination, methionine aminopeptidase activity, Heterograft, postnatal development, Metabolic Concepts, BCRP1, mBAF60c, growth and development, TRANSPL HETEROL, NURF, dysfunctional, dmTAF[[II]]230, Rsc6p, Ca tail of pancreas, Ca head of pancreas, U2 snRNP, diseases, tumour of pancreas, Mother Cells, Concepts, 2, diseases and disorders, tcf3a, Metabolism Concept, Phenomenon, peptidase M activity, pancreas tumour, adenomas, treatment, bcrp1, neoplasm of pancreas, dISWI, rabGAPLP, human disease, L-methionine aminopeptidase activity, reference sample, TFIID TAF250, SWI2, Tcf3a, cel, catabolism, neoplasm (disease), U2 snRNP B'' protein, SNF2L, RabGAP-5, HNF3alpha, metabolic process resulting in cell growth, DNA Methylomes, tumor of pancreas, CA, Epigenomic, genetic, Hnf-3a, Bcrp1, SWI, ACF, Xenotransplantations, malignant neoplasm, RUSC3, carcinoma of the pancreas, ISW, disease management, CG8625, biotransformation, Homo sapiens disease, stage, HNF3A, Catabolism, pancreatic tumour, pancreas neoplasm, pancreas tumor, malignancy, dTAF[[II]]230, Process, Methylomes, pancreatic cancer (not islets), malignant neoplasm of body of pancreas, malignant neoplasm of pancreas, metabolism resulting in cell growth, familial, fs(1)A1621, MYH-associated polyposis, autosomal recessive familial adenomatous polyposis, TAF200, Maps, cancer of the pancreas, RNA-seq, malignant pancreatic neoplasm, TAFII-250, TAF250/230, liz, Tcf-3a, partial functionality, Programs, Hnf3a, TAFII250, ductal adenocarcinoma of the pancreas, Colony-Forming Unit, Stem Cell, D14S1460, fs(1)1621, Diseases, organ system cancer, tumor of the pancreas, Chemotherapy, Genetic Materials, secretion, pancreatic duct cancer, pancreatic carcinoma, PANCREATIC NEOPL, Pancreatic, C78287, Methylome, Heterologous Transplantations, Genetic Material, CHRAC, CG4528, autosomal recessive, Mother Cell, DmelCG8625, MUTYH-associated polyposis, MUTYH-related AFAP, pancreatic duct adenocarcinoma, RUTBC3, Xenotransplantation, Drives, resistant, neoplasm of the pancreas, exocrine pancreatic carcinoma, growth pattern, Transplantation, Epigenetic, malignant neoplasm of head of pancreas, non-developmental growth, Stem, BRG1-associated factor 60C, Colony Forming Units, Xenografts, lacks function of type, TCF3A, CG17603, pancreas carcinoma, TAF[[II]], Pancreas, human, low functionality, RABGAP5, cancer of pancreas, disease, tumour of the pancreas, malignant neoplasm of the pancreas, Ca body of pancreas, Taf250, Material, SR3-5, Cells, multiple colorectal, MUTYH-related attenuated familial polyposis coli, Cistron, inherited genetic, DNA, Epigenetics, PNCA, cancer, TAF230, DNA Methylome, anon-WO0172774.178, other disease, L2bp1/Baf, d230, 1500001J14Rik, NEOPL PANCREATIC, human being, 60 kDa BRG-1|Brm-associated factor subunit C, tFoxA1, Processes, cell type cancer, Neoplasms, Colony-Forming Units, developmental stage, Progenitor Cell, impaired, Gene, dTAFII250, pancreas, U1-A, Metabolic Processes, pancreas cancer, Transplantations, EfW1, pancreatic ductal adenocarcinoma., heterologous transplantation, p140/ISWI, fs(1)A16121, dmTAF1, Taf230, Metabolism, dBAF, resistance, foxa1, disease or disorder, NURF-140, Whole Transcriptome Shotgun Sequencing, PDAC, neoplasm, dNURF, Metabolism Phenomena, Progenitor, malignant tumour, familial adenomatous polyposis, MAP, TAF250, PANCREAS NEOPL, carcinoma of pancreas, hnf3a, Taf200, dTAF[[II]]250, banf1, Genetic, SNF, Snf, cell, iswi, familial adenomatous polyposis 2, ligand, dysfunction, Heterografts, Mother, Metabolic Concept, Taf1p, NGPS, man, ISWI, non-neoplastic, autosomal recessive multiple colorectal adenomas, dTAF250, pancreatic ductal carcinoma, time of survival, CG7380, disorder, SNF/D25, TAF, constitutitional genetic, anon-EP1279744.124, Heterologous, Controlled, MUTYH-related attenuated familial adenomatous polyposis, NURF140, data, Controlling, Colony Forming Unit, TAF[[II]]250, D25, MUTYH-Associated Polyposis, degradation, malignant, pancreatic ductal adenocarcinoma, Progenitor Cells, pancreatic neoplasm, disorders, L2bp1|Baf, snRNP B'', l(3)84Ab, medical condition, BG:DS00004.13, pancreas neoplasm (disease), Cistrons, Cell, Pancreas Neoplasm, ductal adenocarcinoma of pancreas, pancreas ductal adenocarcinoma, dTAF230, Concept, Metabolic Phenomena, development, Metabolism Concepts, MT, survival, XENOTRANSPL, p230, malignant neoplasm (disease), MUTYH-related attenuated FAP, chemical analysis, Phenomena, Neoplasm, TAF[[II]]250/230, condition, TFIID, metabolism, DmelCG7380, Metabolic Phenomenon, Taf[[II]]250, malignant neoplasm of tail of pancreas, pancreatic tumor, multicellular organism metabolic process, primary cancer, TAF[[II]]230, biodegradation, Epigenomes, Metabolic, malignant neoplasm of duct of Wirsung, 2210409C08Rik, p140, postnatal growth, pancreatic cancer, exocrine pancreas carcinoma, carcinoma of exocrine pancreas, HETEROL TRANSPL, BAF60C, patient, TAF[II]250, snf1621, MYH-Associated Polyposis, malignant tumor, Pancreatic Neoplasms, SNF2L1, having decreased function, single-organism metabolic process, Baf, fatty acid metabolism, DmelCG17603, BAF, pancreatic tubular adenocarcinoma, malignant neoplastic disease, DEL, SNF2LB, MAP syndrome, Nurf-140, malignant pancreas neoplasm, assay, CRACD3, variable, Pancreas Neoplasms, hereditary, growth, dCHRAC, FAP2, colorectal adenomatous polyposis, TAF1, AnabolismPXD038216falsepbSMARCD3 is a key epigenetic dependency for pancreatic adenocarcinomaPancreatic ductal adenocarcinoma (PDAC) is a disease characterized by extensive resistance to conventional therapies, making clinical management a significant challenge. As cancer progresses, developmental signals are often aberrantly re-activated, driving the self-renewal of cancer cells and fueling therapy resistance. To understand the epigenetic regulators that may be required to sustain these aggressive cells, we carried out a focused screen and identified SMARCD3 as a new functional dependency in pancreatic cancer. SMARCD3, a subunit of the SWI/SNF nucleosome remodeling complex, was uniquely up-regulated in PDAC stem cells and amplified in human cancer. Using a dual-recombinase model of pancreatic cancer, we showed that stage-specific conditional genetic deletion of Smarcd3 preferentially impaired growth of established tumors, improving survival and synergizing with chemotherapy. Consistent with this, SMARCD3 was required for the in vivo propagation of patient-derived xenografts. Mechanistically, we found that SMARCD3 is incorporated in the BAF complex variant of SWI/SNF. Using comprehensive ChIP-seq analysis to map the SMARCD3-dependent epigenome we showed that Smarcd3 inhibition drives global losses in histone acetylation and BAF binding at active enhancers co-bound by FOXA1. Integrating this with RNA-seq analysis, we found that SMARCD3-BAF regulated a network of genes implicated in diverse programs converging on lipid homeostasis. Specifically, Smarcd3 deletion in vivo inhibited fatty acid metabolism, which is known to be enriched within therapy-resistant cancer cells. These data collectively identify SMARCD3 as a critical dependency in PDAC and link SWI/SNF with the epigenetic control of cell state and metabolism in PDAC.Fri Nov 18 16:59:00 GMT 2022MSV000090744